NCT02941809

Brief Summary

More than 2 million individuals in the United States have an Opioid Use Disorder (OUD). Methadone maintenance treatment is the gold standard of medication-assisted treatment for OUD, but high-dose methadone is associated with cardiotoxicity and respiratory complications, among other side effects. These adverse effects make enhancing the effectiveness of lower doses of methadone an attractive therapeutic goal. Long recognized for its capacity to enhance treatment outcomes for a wide range of neuropsychiatric disorders including pain, the placebo effect offers an as-yet untested avenue to such an enhancement. This approach is particularly compelling given that individuals with substance use disorder tend to have higher salience attribution, and may thereby be more sensitive to placebo effects. Our study combines two promising clinical methodologies-open-label placebo and conditioning-to investigate whether placebo effects can increase the effective potency of methadone in treatment-seeking OUD patients.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
133

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Dec 2017

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 19, 2016

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 21, 2016

Completed
1.1 years until next milestone

Study Start

First participant enrolled

December 5, 2017

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 31, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2020

Completed
Last Updated

August 11, 2020

Status Verified

August 1, 2020

Enrollment Period

2.7 years

First QC Date

October 19, 2016

Last Update Submit

August 7, 2020

Conditions

Opioid-use DisorderOpioid-Related Disorders

Keywords

medications for opioid use disordermethadone

Outcome Measures

Primary Outcomes (1)

  • Three-month dose of methadone

    Mean dose of methadone at 3 months (90 days) post-baseline (entry into treatment) will be evaluated for each of the two arms.

    Three months (90 days)

Secondary Outcomes (9)

  • Treatment Retention

    90 and 180 days post-baseline (entry into treatment)

  • Total number of days retained in treatment

    One year post-baseline (entry into treatment)

  • Mean number of days of self-reported drug use

    Baseline (entry into treatment), two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline.

  • Urine Testing- Quick-tox Screen

    Baseline

  • Craving assessment

    Baseline (entry into treatment), two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline.

  • +4 more secondary outcomes

Other Outcomes (8)

  • Pain Catastrophising Scale (PCS)

    Baseline (entry into treatment), and 1- and 3-months post-baseline

  • Compliance

    Two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline

  • Methadone side effects checklist

    Two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline

  • +5 more other outcomes

Study Arms (2)

Open-Label Placebo (OLP)

EXPERIMENTAL

Participants who are randomly assigned to group OLP will receive placebo pills. In Phase 1 of the study (first two weeks), participants in this group are given one pill, to be taken concomitant with the methadone. In Phase 2 (3 weeks up to 3 months), OLP participants continue to take the single (morning, or AM) pill, and are given a second pill in a bottle as a take-home. OLP participants will meet with the study team at five time points: at baseline (entry into treatment), 2 weeks post-baseline, and 1-, 2- and 3-months post-baseline.

Behavioral: Open-Label Placebo (OLP)

Treatment as Usual (TAU)

NO INTERVENTION

Participants assigned to TAU will not be given placebo pills, but all interactions with the study team (5 meetings total) will be matched in frequency and length.

Interventions

Open-Label Placebo (OLP)BEHAVIORAL

We are designating this as a behavioral intervention for two reasons: (1) the placebo pill is physiologically inert and is not classified under FDA regulations; and (2) other studies have demonstrated that the efficacy of the placebo pill is strongly dependent on the participants' anticipation of an effect. We are presenting the pill's efficacy in an open and transparent way to the participants, but using a positive frame. We feel that this qualifies the placebo pill use as a behavioral intervention, in the same general category as exercise or relaxation.

Open-Label Placebo (OLP)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Adult (age 18 or over)
  • Newly-admitted to the methadone treatment program

You may not qualify if:

  • Pregnancy
  • Transfers- patients who have initiated methadone treatment course at another methadone treatment facility
  • Hospital transfers- patients who initiated methadone treatment course in a hospital setting
  • Criminal justice referral

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Maryland Methadone Treatment Center

Baltimore, Maryland, 21201, United States

Location

Related Publications (3)

  • Belcher AM, Cole TO, Greenblatt AD, Hoag SW, Epstein DH, Wagner M, Billing AS, Massey E, Hamilton KR, Kozak ZK, Welsh CJ, Weintraub E, Wickwire EM, Wish ED, Kaptchuk TJ, Colloca L. Open-label dose-extending placebos for opioid use disorder: a protocol for a randomised controlled clinical trial with methadone treatment. BMJ Open. 2019 Jun 21;9(6):e026604. doi: 10.1136/bmjopen-2018-026604.

    PMID: 31230007BACKGROUND

  • Cai NS, Quiroz C, Bonaventura J, Bonifazi A, Cole TO, Purks J, Billing AS, Massey E, Wagner M, Wish ED, Guitart X, Rea W, Lam S, Moreno E, Casado-Anguera V, Greenblatt AD, Jacobson AE, Rice KC, Casado V, Newman AH, Winkelman JW, Michaelides M, Weintraub E, Volkow ND, Belcher AM, Ferre S. Opioid-galanin receptor heteromers mediate the dopaminergic effects of opioids. J Clin Invest. 2019 Mar 26;129(7):2730-2744. doi: 10.1172/JCI126912.

    PMID: 30913037BACKGROUND

  • Belcher AM, Cole TO, Massey E, Billing AS, Wagner M, Wooten W, Epstein DH, Hoag SW, Wickwire EM, Greenblatt AD, Colloca L, Rotrosen J, Magder L, Weintraub E, Wish ED, Kaptchuk TJ. Effectiveness of Conditioned Open-label Placebo With Methadone in Treatment of Opioid Use Disorder: A Randomized Clinical Trial. JAMA Netw Open. 2023 Apr 3;6(4):e237099. doi: 10.1001/jamanetworkopen.2023.7099.

    PMID: 37043203DERIVED

MeSH Terms

Conditions

Opioid-Related Disorders

Condition Hierarchy (Ancestors)

Narcotic-Related DisordersSubstance-Related DisordersChemically-Induced DisordersMental Disorders

Study Officials

  • Annabelle M Belcher, PhD

    University of Maryland, Baltimore

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor of Psychiatry

Study Record Dates

First Submitted

October 19, 2016

First Posted

October 21, 2016

Study Start

December 5, 2017

Primary Completion

July 31, 2020

Study Completion

July 31, 2020

Last Updated

August 11, 2020

Record last verified: 2020-08

Data Sharing

IPD Sharing
Will not share

Locations

US(1)